ASPARAGUS, STINKY PEE, AND SCIENTIFIC CURIOSITY

I was recently enjoying a nice dinner with a few close friends of mine. Our conversations are often less than delicate, so it was no surprise that talk soon became a little tactless. The subject turned to the unpleasant yet inevitable consequences of our meal that would visit each of us within a few hours. No, we weren’t talking about beans (the so-called “musical fruit”), but about asparagus, a seemingly benign green delicacy that goes especially well with hollandaise sauce. Strangely, one member of our group had no idea what we were talking about, despite describing asparagus as her favourite (and also oft-consumed) veggie. Eventually, I had to spell out for her what I assumed anyone who had ever tried asparagus must know – it tastes great, but later gives its consumer horribly, wretchedly, and obviously stinky pee. Of the six people at dinner, she was the only one who had never noticed such a phenomenon. She promised to pay special attention on her next bathroom visit, and eventually reported back to the group: no stink.

Being a geeky scientist type who also happened to be taking biochemistry, I supposed that my friend differed from the rest of us in how her body broke down the asparagus – in other words, that she metabolised some component differently. The food we eat is digested, both mechanically and chemically, into numerous minute components; the fate of these components can include storage for later use, immediate recycling, or excretion. Complex proteins called enzymes catalyze these processes, and as is the case with all our body’s proteins, they derive from a blueprint in our genetic code, or DNA. I had learned of genetic errors of metabolism in biochemistry class, including the very literally named maple syrup urine disease, a condition that imparts a sweet odour to the urine (along with a number of other far more severe symptoms). Remembering this disease prompted my suspicion that a genetic variation likely accounted for whatever my friend didn’t smell.

Surveys can be helpful tools in science, but to draw meaningful conclusions from the results, scientists must use a large enough sample size to ensure their numbers are significant (i.e. they’re not biased, a fluke, etc.) Clearly, my dinner-table survey was not statistically relevant, so I set to work. I began asking everyone I know if they noticed anything unusual in the hours after eating asparagus. I learned a number of things:

1) Most people do not eat asparagus often enough to even remember when they last had it;

2) Many people had no clue what I was talking about, but when prodded to have some asparagus for dinner and report back, the majority said something along the lines of “Oh, that’s where that smell comes from!”

3) Some people prefer not to discuss the scent of their pee, even in the name of science;

4) I don’t have enough friends to gather sufficient data for any kind of survey.

Nevertheless, I will report that of the 22 asparagus-eaters willing to discuss the matter with me, three swore up and down they had no stink to report. That’s about 14%, but given the margin of error inherent to my small sample size, it doesn’t mean much. (Interestingly, one of the non-stinkers was my own mother – presumably, I inherited the stinky trait from my father.)

My survey being a bit of a bust, a turned to another tool in the scientist’s arsenal: research. (Truth be told, I really should have gone here first.) It turns out that many before me have been riddled by the mystery that is asparagus-induced stinky pee (or malodorous urine, as those fancier types call it). Incredibly, some scientists have been curious enough to actually study the phenomenon. Indeed, some 50 years ago, a study found about half of the British population to be “excretors” – people whose bodies make the foul-smelling compound (1). It was later found that, as with any genetic trait, frequency varies with population; a study of French citizens found all subjects produced the smelly compound (2).

So what exactly is this stinky chemical? The answer is a matter of dispute, with a surprising number of scientists weighing in. There are a number of fancy machines and complex techniques that are used to identify the chemical makeup of a substance, but none of them will tell you which of the numerous chemicals in a urine sample is causing a certain smell! A veritable laundry list of chemicals has been proposed as the offender, with some suggesting it may be a combination of many. All agree it is likely some sulphur-containing compound, one likely contender being asparagusic acid (3).

Reading this paper, you may have noticed a rather serious error in my early logic. My stinky pee hypothesis was based on what I was familiar with; that is, metabolic processes and variations. However, had I been studying sensory processes (particularly, our sense of smell) instead of metabolic biochemistry, might I have considered a different theory? Isn’t it possible that we differ not in our ability to make a certain compound, but in our ability to smell it? The answer to this question, I discovered, is yes. Perhaps operating on the same bias as I was, early studies of the stinky pee phenomenon had subjects eat asparagus, do their business, and report any smell (or lack thereof) to the researchers. Those reporting no smell were then designated non-excretors, and the study results based on these reports. However, it never occurred to the researchers to have someone else smell the urine samples, ideally, someone known to be able to identify the smell. Some of the supposed non-excretors may have indeed been producing the offensive odour, but not been able to smell it. This error underscores the importance of considering all possible solutions when faced with a scientific puzzle.

A 1980 study examined the possibility that anosmia (the inability to smell the compound) might actually account for those though previously to be non-excretors. Interestingly, the results showed that, indeed, some people are simply unable to smell the foul odour, no matter how strong it may be (4). Thus was identified a new category of people, the “nonpercievers”, with those of us able to smell the stench called “perceivers”.

So is the mystery now solved? Are we all stinkers, but only some of us smellers? Not exactly. The 1980 study found that, as earlier reported, nonexcretors do exist. But these people were not exclusively nonpercievers – some could sense the smell in other’s urine. Conversely, some excretors were unable to detect the compound in urine others had identified as outright putrid. Apparently, this riddle, like much of genetics, has more than one answer. We have tens of thousands of genes, each wielding influence over one or several traits. From an evolutionary perspective, it’s hard to imagine why some of these genes exist; really, what survival advantage is gained with the ability to smell asparagus pee stink? And why should some of us make the compound while others don’t? I have no answers to these questions, but do know that genetics can make for fascinating dinner conversation, particularly when the meal includes asparagus.

References
1) Allison AC & McWhirter KG. Two unifactorial characters for which man is polymorphic. Nature. 1956 Oct 6; 178 (4536):748-9.

2) Mitchell SC. Asparagus and malodorous urine. Br J Clin Pharmacol. 1989 May; 27(5):641-2.

3) Mitchell SC. Food idiosyncrasies: beetroot and asparagus. Drug Metab Dispos. 2001 Apr; 29 (4 Pt 2):539-43.

4) Lison M, Blondheim SH, & Melmed RN. A polymorphism of the ability to smell urinary metabolites of asparagus. Br Med J. 1980 Dec 20-27; 281 (6256):1676-8.

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(REPRINTED FROM ISSUE ONE, JUNE 6th, 2005)